Human platelet activation in the absence of aggregation: a calcium-dependent phenomenon independent of thromboxane formation.
In response to ionophore A 23187, thrombasthenic and EDTA-treated control platelet-rich plasmas (PRP) undergo a change in light transmission (LT) accompanied by a normal 14C-serotonin (5HT) release and thromboxane (TX) synthesis in the absence of aggregation. Ultrastructural qualitative electron microscopy revealed central apposition of organelles and loosely packed platelets in both models, while a central gel mass appeared only in thrombasthenic patients. Quantitative analysis of this ultrastructural change showed an increase in the elongation and a decrease in the circularity coefficients of thrombasthenic platelets, indicating a shape change with pseudopod formation, while EDTA-treated platelets underwent a shape change in the absence of pseudopod formation. Morphometric analysis showed that the ionophore caused extensive degranulation in both types of platelets (decrease of the granule volume), which occurred in the presence of contraction of thrombasthenic PRP (decrease of the SCS plus granule volume) but in its absence in EDTA-treated platelets. The change in LT was not inhibited by aspirin, suggesting a dissociation between release of 14C-5HT and TX formation. Moreover, it was not inhibited by creatine phosphate plus creatine phosphokinase, prostaglandin E1, or cytochalasin and/or colchicine. It was not dependent on ADP, cAMP, or the integrity of microfilaments and microtubules. However, chlorpromazine, TMB 8, and dibucaine, which interfere with intracellular membrane transport of Ca2+, inhibited this platelet activation (change in LT, 14C-5HT release and TX synthesis.
D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000648:ultrastructure; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D006801:Humans; D008854:Microscopy, Electron; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D012701:Serotonin / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism*; D013931:Thromboxanes / Q000378:metabolism*
D013931:Thromboxanes; D012701:Serotonin; D000001:Calcimycin; D013929:Thromboxane B2; D001241:Aspirin; D002118:Calcium